Overweight and obesity are now recognized as leading causes of diseases such as type 2 diabetes, hypertension, hyperlipidemia, and ultimately, cardiovascular disease. Despite the serious consequences, roughly two thirds of Americans are presently classified as overweight, and about one third are classified as obese. Weight loss via lifestyle modification and pharmacotherapy can promote improvement in many of these obesity-related conditions. This review addresses recent advances in pharmacotherapy for the management of obesity and obesity-related co-morbidities, with a focus on the management of obesity specifically in individuals with type 2 diabetes. Emphasis is also placed on a proposed paradigm shift from the glucose-centric to the weight-centric management of type 2 diabetes mellitus.