Summoners may choose two from a selection of 5 Paths, which are thematically similar to the three Mastery Trees from previous seasons. Each Path is structured like a Mastery Tree, with a number of slots that each have a selection of unique and mutually exclusive Rune options, with the player's Primary Path choice having additional slots, including a Keystone slot.
The new system is available to summoners of all levels at no cost and can be customized in champion select, similar to Masteries. However, players may only have a limited number of saved pages but may purchase additional pages for convenience.
In his youth, thousands of years ago, Ryze witnessed the discovery of the first World Rune, as well as many more in the decades that followed. Believed to be a font of The Makers's might, conflict soon erupted over their control. This conflict escalated into the great Rune Wars, which erased Ryze's boyhood village of Khom, Shurima, from reality.
Sobered by the threat of annihilation, Ryze and his mentor manage to convince many of the World Rune's holders into sealing their World Runes beyond the reach of man. But many refused. After the death of his mentor, it fell to Ryze to continue the quest with only an ancient scroll for guidance.
Forward to the present day, the World Runes have begun to emerge once more, and the world has forgotten the price of wielding them.
Summoners may choose two Paths: one Primary and one Secondary. You may not pick the same path twice. There are five paths to choose from:
Precision (Improved attacks and sustained damage)
Domination (Burst damage and target access)
Sorcery (Empowered abilities and resource manipulation)
Resolve (Durability and crowd control)
Inspiration (Creative tools and rule bending)
The Primary Path has one Keystone slot and 3 Lesser slots, while the the Secondary Path has a choice of 2 of the 3 Lesser slots. Each individual slot provides a unique selection of runes, similar to the branches of the former Mastery trees. You also gain an additional bonus based on the combination of your paths, referred to as a Set Bonus or Trait.
The Set Bonus is an additional passive based on the combination of your chosen paths, although not all combinations have distinct effects. The set's Title is currently only used within the in-game client, with the passive being unnamed when viewed within the out-of-game Rune Inventory.
The Merciless Elite
The Brazen Prefect
The Eternal Champion
The Twisted Surgeon
The Aether Blade
The Immortal Butcher
The Ingenious Hunter
The Incontestable Spellslinger
The Ancient One
The Imperious Behemoth
The Arcane Colossus
The Enlightened Titan
The Elegant Duelist
The Ruthless Visionary
The following substitutions will automatically be made where applicable:
These substitutions are noted in chat when the game starts.
Players cannot begin creating/editing rune pages until summoner level 11, but all accounts have access to 5 Preset Pages from level 1 that cannot be edited. The ability to hide Preset Pages was added in V7.23.
As with the previous system, accounts begin with 2 slots for personalized rune pages and may purchase the convenience of additional pages in the store for 590 or 6300. Any Rune Pages the player owned in the previous system were transferred across to the new system, in addition to the compensation received.
In the former system there was a limit of maximum 20 rune pages per account, but this is no longer true. The current limit is 25 Rune Pages as of Patch V7.22. The presets are not counted toward the limit.
Presets and Example
Inspiration: The Timeless (Inspiration + Resolve)
Precision: The Prefect (Precision + Sorcery)
Domination: The Executioner (Domination + Precision)
During development, Precision and Sorcery were originally going to be Primary-only. 
Runes and their surrounding areas have distinct visual appearances similar to Runeterran factions, which may be intentional and reflect the real-world location of the World Runes:
Precision - Golden cityscape of Demacia or Shurima
Domination - Noxian fortification
Sorcery - Mountains of The Freljord, Mount Targon or Icathia
Resolve - Riverlands of Demacia, Ionia or southern Freljord
Inspiration - Beneath the heavens atop Mount Targon
The following statements generalize the changes made to compensate the loss of AD from Marks and Health/Armor from Seals, which were almost unanimously used due to the lack of options (and thus the game has been balanced, for example, around most champions having +9 Armor from Seals). The exact values may vary for specific cases, as Riot also took this opportunity to better distinguish classes (e.g. tanks from non-tanks; ranged from melee), as well as buff/nerf specific champions.
AD champions had the base damage on their abilities increased by 5.
Ranged AD champions also had their base attack damage increased by 8.
Most champions had their base armor increased by 9.
Most mages had their base health increased by 12 (+12), instead. Primarily excepting junglers.
Melee supports had their base armor increased by 20, instead.
Riot has stated that they already have a number of additional runes in the works that will not be finished before the initial release.
Players may also see additional paths in the future, although none are currently in development and they would not be added outside of the mid- or pre-season patch.
There are 43,740 possible rune combinations, factoring that:
There are 20 possible combinations of the 5 Rune Paths.
There are 81 possible combinations of primary runes.
There are 27 possible combinations of secondary runes.
Every rune that gives bonus Adaptive AD or AP, will always grant about 60% of the amount of AP as AD, or about 166.6% of the amount of AD as AP.
New Effect: You can now swap your spells anywhere, not just at the store.
New Effect: If replacing a Summoner Spell that is on cooldown, the newly acquired Summoner Spell is unavailable to cast for a time equal to 50% of the remaining cooldown of spell that is being replaced.
New Effect: After collecting 100 Soul Essence, the timer to trigger the empowered attack increases to 300 seconds.
Editor Note - Correction: Apologies. The tooltip previously listed that the AD or AP ratio was Adaptive, but this was incorrect. Rather, it scales with both and it's actually the Damage Type that is adaptive.
Editor Note - Correction: Apologies. The tooltip previously listed that it reduced mana costs, but this was incorrect. Rather, it refunds mana spent. This is a subtle difference, but prevents abilities from being activated if you do not have sufficient mana to start with.