Street Missions or Random Encounters are missions performed for minor characters found standing on the streets throughout Grand Theft Auto IV. The availability of a street mission is indicated by a small blue person-shaped icon, also called a friend icon, on the radar when one is in close proximity. Street missions provide Niko with small storylines and minor missions. The "No More Strangers" achievement/trophy for Grand Theft Auto IV involves locating each of the random characters helping each one out in a street mission at least once. Most of the random character missions are required for 100% completion.

Introduced to Niko during the Shadow mission, Niko helps Badman later in the game when Badman's business is being threatened by a Russian gang. They take out the Russians together, and Niko receives $500 for the trouble.

When spared by Niko in the Ruff Rider mission, Cherise Glover returns to ask for help with an abusive boyfriend. Niko beats her boyfriend and warns him to stay away from Cherise. Niko also has the option to kill the boyfriend. In this case Cherise would be horrified and run away. In either case, she is not heard from again.

Jeff is a wealthy but paranoid business man who asks you for help believing that his wife Shirley is cheating on him. Niko investigates and determines that she is not. Despite reassurances, Jeff stabs his wife 50 times with a kitchen knife, hiding her body in a Blista Compact. Niko dumps the car for him in the Humboldt River. Later in the game, after Jeff has quickly remarried, he again thinks his new wife is cheating. He asks Niko to kill her. Niko refuses. Jeff runs out into the street and is run over by a Turismo.

Sara is a random character who is quite concerned about her appearance and claims to be part of the fashion scene. In her first meeting with Niko, she asks him for a ride home from Suffolk Algonquin to Varsity Heights. When Niko takes her home, she introduces him to her ex-husband, saying that she has been sleeping with Niko and that he's "hung like a rhino". The ex-husband attacks Niko, leaving Niko with several choices. Their second encounter, Sarah asks Niko to pick up a package at Perseus. To Niko's surprise, the clerk asks him for $500 before he will hand it over. Whether Niko pays for the package, bullies it away, or kills the clerk, deliver the package to Sara for a $1,000 reward.

Mel appears as a drunk in the first Vlad missions in Comrades Bar. Niko meets up with a sober Mel later in the game. Mel says he has cleaned up his life and is trying to pay everyone back from his drinking days. Niko defends him in a fight against some men Mel owes money to and is never seen again.