The discovery of CO emission (Wilson, Jefferts & Penzias 1970) 25 years ago opened a major new astronomical window which has led to important advances in many areas of Galactic and extragalactic astronomy. The strength and ubiquity of the CO lines, CO isotopic lines, and other millimeter transitions have provided extraordinary diagnostics for studying molecular interstellar matter in the Milky Way and in external galaxies. All dense interstellar gas is molecular hydrogen, H2 (Solomon & Wickramasinghe 1969), due to the sharp transition from HI to H2 caused by the self-shielding of H2 from photodissociation by absorption in the Lyman bands followed by emission downward into the continuum. The balance between formation on grains and photodissociation yields an optically thick self-shielding layer in all clouds where the total neutral hydrogen density n(H + 2H2) > 100 cm−3. Since H2 itself has no radio or millimeter transitions and HI is absent, abundant minor constituents like CO become the main tracer of H2. All current star formation takes place in molecular clouds since the first stage of star formation is the formation of high-density interstellar clouds. Molecular clouds and particularly giant molecular clouds (GMC), with masses > 1 x 105 M⊙, the most massive objects in the Galaxy are a major component of the interstellar medium.