Lipid droplets (LDs) were originally described in milk by van Leeuwenhoeck in 1674. Although over 300 years have passed since this original observation, many fundamental questions about LDs remain unaddressed. Until recently, very few of the surface proteins had been characterized and the functions of LDs, aside from their presumed role as neutral lipid storage depots, remain unknown. To better understand LDs, we and others have recently carried out several proteomic studies using a combination of purified LDs and mass spectrometry (MS) protein identification. Many of the proteins which have been newly identified by this approach can be divided into two functional categories: lipid synthetic/metabolic enzymes and membrane trafficking proteins. Importantly, different laboratories investigating a variety of different cell types have found similar results. These findings strongly suggest that LDs are a complex, metabolically active organelle that may participate in lipid synthesis and trafficking. This review will describe progress in identifying these proteins and will also discuss the potential implications for the function of animal LDs. For detailed information on other aspects of LD biology, please read the review from Denis Murphy.