Observations of the star formation activity in galaxies has revealed a relationship between the star formation rate and the surface density of the gas, especially when one looks at the cold, H2-dominated phase.  Although the physical process behind this phenomenon is not fully understood, it has been used by the galaxy formation community as a sub-grid model in the their numerical simulations.  While this might work on large scales, and for ’standard’ galaxy types, it fails when we look at the detailed structure within the galaxies.  Milky Way star formation studies attempt to work from the bottom up, rather than the top down. In my talk, I will discuss recent results from numerical simulations and observational studies that shed light on the large-scale processes that regulate the star formation process in galaxies. From a theoretical viewpoint, I will compare the relative role of various feedback processes, such as photo heating of the ISM, supernovae and cosmic rays. On the observational side, we will use Milky Way studies to show that much of the observed molecular gas in galaxies may not be involved in the star formation process at all.