Obesity and its associated complications have reached epidemic proportions in Western-type societies. Concomitantly, the obesity incidence in developing countries is increasing. One hallmark of obesity is the differentiation of pre-adipocytes into mature triglyceride-loaded adipocytes present in subcutaneous and visceral adipose tissue depots. This may ultimately lead to dysfunctional adipose tissue together with detrimental changes in the profiles of (pre-)adipocyte-secreted proteins, known as adipokines. Obesity-induced alterations in adipokine profiles contribute to the development of obesity-associated disorders. Consequently, the interest in the molecular events responsible for adipose tissue modifications during weight gain and weight loss as well as in the aetiology of obesity-associated disorders is growing. Molecular mechanisms involved in pre-adipocyte differentiation and alterations in adipokine profiles have been examined at the gene and protein level by high-throughput technologies. Independent proteomics studies have contributed significantly to further insight into adipocyte biology, particularly with respect to adipokine profiling. In this review novel findings obtained with adipo-proteomics studies are highlighted and the relevance of proteomics technologies to further understand molecular aspects of adipocyte biology is discussed.