| Reward and imbuing shrines | Marapur | 2 | 1 |
| Rita’s letter | Liberty Bay | -4 | 1 |
| Ritual figurine | Venore | -3 | 1 |
| Ritual stone tablet | Venore | -2 | 1 |
| Ritual sword | Venore | -3 | 1 |
| Robby the Reckless (spawn location) | Carlin | -2 | 1 |
| Rockfalls | Roshamuul | -7 | 1 |
| Ron the Ripper (pirate raid boss) | Liberty Bay | 3 | 1 |
| Room with lava | Boss Lairs | -4 | 1 |
| Rorcs or drillworms and lost dwarves | Ab'Dendriel | Surface | 1 |
| Rotrender | Roshamuul | -1 | 1 |
| Rotspit (spawn location) | Gray Beach | -1 | 1 |
| Rotten Wasteland (Goshnar’s Hatred) | Blue Valley | -3 | 1 |
| Rottin Wood | Kazordoon | Surface | 1 |
| Rotworm Queen (possible spawn location) | Liberty Bay | -3 | 1 |
| Rotworm Queen (spawn location) | Edron | -2, -5 | 3 |
| Rotworms / bog raiders | Edron | Surface | 1 |
| Rotworms and orcs | Dawnport | -1 | 1 |
| Ruins of Nuur | Krailos | Surface | 1 |
| Rukor Zad (spawn location) | Newhaven | -3 | 1 |
| Rusted key fragment (handle) | Venore | -6 | 1 |
| Rusted key fragment (head) | Venore | -6 | 1 |
| Sacred site | Krailos | Surface | 3 |
| Sacrificial altar (use bloodstained scythe to summon Malvaroth) | Roshamuul | -1 | 1 |
| Sacrificial altar (use hellhunter eye to summon Gralvalon) | Roshamuul | -3 | 1 |
| Sacrificial altar (use spellreaper staff totem to summon Twisterror) | Roshamuul | -2 | 1 |
| Safe room | Liberty Bay | -5 | 1 |
| Safe spot | Roshamuul | Surface, -4, -7 | 7 |
| Safety spot | Roshamuul | Surface | 1 |
| Salt Caves (bashmu) | Issavi | Surface | 1 |
| Sample of monster blood | Feyrist | -1 | 1 |
| Sandking boss room | Edron | -8 | 1 |
| Santiago’s hut | Travora | 1, Surface | 2 |
| Sarcophagus with ocarina | Darashia | -2 | 1 |
| Sausage Eating Contest | Nostalgia | Surface | 1 |
| Scarith's soul cage (use ice damage) | The Void | -8 | 1 |
| Scarlett Etzel | Southern Darama | 1 | 1 |
| Scorn of the Emperor | Yalahar | -7 | 1 |
| Scorpion altar | Darashia | -2 | 1 |
| Scorpion’s pincer (small amethyst) | Darashia | -2 | 1 |
| Second room (use explosive barrel) | Oramond | -7 | 1 |
| Secret door (unlock from the other side) | Newhaven | -7 | 1 |
| Secret hole (messages in a bottle required) | Roshamuul | Surface | 1 |
| Serpent spawns / medusas | Travora | -2 | 1 |
| Sewer Problem 1 | Yalahar | -1 | 1 |
| Sewer Problem 2 | Yalahar | -1 | 1 |
| Sewer Problem 3 | Yalahar | -1 | 1 |
| Sewer Problem 4 | Yalahar | -1 | 1 |
| Sewer warden | Rathleton | -1, -2 | 2 |
| Shaburak demons / askarak demons | Edron | -6 | 1 |