Organisms store energy for later use during times of nutrient scarcity. Excess energy is stored as triacylglycerol in lipid droplets during lipogenesis. When energy is required, the stored triacylglycerol is hydrolyzed via activation of lipolytic pathways. The coordination of lipid storage and utilization is regulated by the perilipin family of lipid droplet coat proteins (perilipin, adipophilin/ADRP, S3–12, TIP47 and MLDP/OXPAT/LSDP5). Lipid droplets are dynamic and heterogeneous in size, location, and protein content. The proteins that coat lipid droplets change during lipid droplet biogenesis and are dependent upon multiple factors, including tissue-specific expression and metabolic state (basal versus lipogenic versus lipolytic). New data suggest that proteins previously implicated in vesicle trafficking, including Rabs, SNAREs, and motor and cytoskeletal proteins likely orchestrate the movement and fusion of lipid droplets. Thus, rather than inert cytoplasmic inclusions, lipid droplets are now appreciated as dynamic organelles that are critical for management of cellular lipid stores. That much remains to be discovered is suggested by the recent identification of a novel lipase (ATGL) and lipase regulator (CGI-58), which has led to reconsideration of the decades-old model of lipolysis. Future discovery likely will be driven by the exploitation of model organisms and by human genetic studies.