Maclisp — historical Lisp for ITS and Multics, and the base for a family of dialects that consolidated as the Common Lisp standard. It was used to bootstrap Scheme.
SHRDLU — infamous natural language input and block stacking robot simulation, written in Maclisp.
Lisp machines — were bootstrapped from ITS and Maclisp.
C compiler — written by Alan Snyder; possibly the first created outside Bell Labs.
Macsyma — symbolic manipulation program that was written in Maclisp and made available to researchers on the Arpanet. Macsyma was so important a dedicated PDP-10 was purchased for it, not just once, but twice.
Emacs — was developed on ITS as a set of TECO macros.
The Magic Switch — a piece of hacker lore chronicled in Guy Steele's book Hacker's Dictionary. The book comes from the JARGON file.
Logo — educational programming language began at BBN but greatly enhanced at MIT. ITS hosts many versions for the PDP-10, PDP-11, Apple II, etc. A Small ITS timesharing system was written to run Logo on a PDP-11/45. Marvin Minsky designed the 2500, a dual text and vector display minicomputer for running Logo.
CLU — a programming language by Barbara Liskov that introduced abstract data types way ahead of its times. The CLU group developed the first version of the X Window System.
Zork — was written in MDL/Muddle, the major programming language on the Dynamic Modeling PDP-10. Zork was inspired by (Colossal Cave) Adventure, which is also available on ITS. Together, the two games were instrumental in kicking off text adventure games and interactive fiction.
Maze — 3D game, and possibly the first first-person shooter.
MacHack VI — Greenblatt's chess program was the first computer program to play chess in human tournament competitions and be granted a chess rating.
Spacewar — one of the first video games. First developed on a PDP-1 at MIT. ITS has a much updated PDP-6 version, and consoles made by HAKMEM author Mike Beeler.