Obesity is a global health concern that impacts health, quality of life, and longevity in affected individuals. Comorbid cardiovascular disease, type 2 diabetes, cancer, and other conditions often accompany obesity, and researchers are actively investigating therapeutic strategies to treat obesity and mitigate the health risks associated with excess adiposity. Restrictive nutritional intake and body weight reduction through lifestyle behavioral interventions, bariatric procedures, and highly effective anti-obesity medications are all recommended treatments for obesity. Meanwhile, the caloric restriction that comes with very low-calorie diets can result in changes in body composition, most notably a progressive loss of muscle mass and/or functionality, a process that can be accelerated by aging, underlying metabolic disease, or inadequate protein intake seen with many dietary patterns. While muscle loss was previously understood as a condition only affecting older individuals, this outcome is common in patients with obesity. The term sarcopenic obesity has been used to refer to this condition, and it is now recognized as an important potential complication in all patients with obesity. Dietary challenges that influence overall body composition also have drawn attention to the gut microbiome, a topic of growing interest as there is an increasingly recognized interplay between diet, the metabolic actions of microorganisms in the gut that impact macronutrient and micronutrient production and absorption, and human health. This article will review the current understanding of obesity as a chronic disease, the impact of diet and nutritional therapy on body composition, and the potential relevance of the gut microbiome in this setting.