Regular physical exercise (PE) has been recognized as one of the most powerful lifestyle strategies used to mitigate overweight and obesity. In this context, white adipose tissue (WAT) plays a pivotal role as it is the largest site of storage and release of excess energy, thus participating in important metabolic, endocrine and inflammatory functions, which are intricately linked to the etiology and pathophysiology of obesity-associated chronic diseases. Moreover, current literature reports that PE, besides reducing visceral fat accumulation, also mitigates obesityinduced dysregulated adipokine synthesis and release, resulting in systemic metabolic improvements through beneficial dynamics changes in WAT. More recently, PEinduced hormone secretion by skeletal muscle has been described as a potential mechanism for inducing a brown fat-like phenotype in WAT. Thus, the modulatory impact of PE on WAT may also occur through the cross-talk between skeletal muscle and adipose organ axis. In this chapter, we focused on the overall impact of PE on WAT morphological, metabolic and inflammatory features, on the cross-talk between skeletal muscle and WAT as well as on the potential mediators of this process, providing an overview of the effects of PE on the obesity-related underlying pathways.