Human obesity and its complications are an increasing burden in developed and underdeveloped countries. Adipose tissue mass and the mechanisms that control it are central to elucidating the aetiology of obesity and insulin resistance. Over the past 15 years tremendous progress has been made in several avenues relating to adipose tissue. Knowledge of the lipolytic machinery has grown with the identification of new lipases, cofactors and interactions between proteins and lipids that are central to the regulation of basal and stimulated lipolysis. The dated idea of an inert lipid droplet has been appropriately revamped to that of a dynamic and highly-structured organelle that in itself offers regulatory control over lipolysis. The present review provides an overview of the numerous partners and pathways involved in adipose tissue lipolysis and their interaction under various metabolic states. Integration of these findings into whole adipose tissue metabolism and its systemic effects is also presented in the context of inflammation and insulin resistance.