The Lost

Many of the game's items provide no benefit to The Lost as they either provide bonuses to health or trigger their effect upon taking damage.

Resurrection items like Dead Cat will still work with the Lost, but the life number does not appear on the HUD.

General Strategies

Before attempting runs with The Lost, it is recommended to unlock the Stop Watch (by donating 999 coins to the Donation Machine). This will allow for a significantly increased chance of avoiding projectiles and enemies.

The Lost will absorb Soul, Black and Eternal Hearts by picking them up, but will not gain any health from them. It is recommended to avoid picking them up in case a D20 or a Dice Room (with 2 dots) is found later on.

Positive items

All items granting invulnerability or any kind of shield are very useful in tough rooms and bosses.

Defensive items like Infamy, Trinity Shield and any orbitals can help.

Items that inflict crowd control status effects such fear, slow or petrification can be useful. On the other hand, some players dislike these items because it can make enemies move in unpredictable ways.

D4 or D6 can reroll negative or useless items into something useful, while D20 can do the same with pickups. D100 acts like the three combined.

After multiple re-rolls, the D4 and D100 can be counterproductive. If the item pools are depleted, they will only give The Lost Breakfast.

Dead Cat grants nine extra lives without any side-effect. It also counts as one of the three items required to transform into the powerful Guppy.

The Lost can enter a Curse Room if the player intents to bet on a Dead Cat being inside of the room,. The multiple lives granted will be able to negate an immediate dead, and therefore the end of the run, by the Curse room doorframe damage.

Goat Head is one of the best items to get early; it will ensure that The Lost can get plenty of Devil Room items.

Gnawed Leaf can be a game-changer for a cautious player, combined with orbitals or bombs against melee or immobile enemies.

Holy Mantle protects The Lost from one hit per room, allowing him to survive a run-ending mistake.

Lost Contact is very effective, especially against "bullet-hell" boss fights like It Lives.

Pyromaniac grants immunity to explosions, making it useful should the player have explosive items such as Ipecac or Epic Fetus. It also protects against troll bombs and stomp attacks.

When combined with the otherwise negative item Kamikaze!, Pyromaniac provides permanent invulnerability as long as the player keep pressing the active item key.

Spectral Tears make a great synergy with flight, allowing The Lost to shoot over obstacles, which block most monsters projectiles and attacks.

Whore of Babylon is always active after being obtained.

???'s Only Friend allows The Lost to consistently remain in a safe place, such as above a rock, while using the controllable familiar

...