The consumption of coffee and caffeine (1,3,7-trimethylxanthine) is part of many cultures worldwide. Their properties include serving as a neurostimulant aid, enhancing energy substrate levels, and improving general exercise performance. Both present therapeutic effects that can also be used to control chronic and metabolic diseases due to four mechanisms: adenosine receptor antagonism, increased catecholamine concentrations, a phosphodiesterase inhibitor, and a stimulator of calcium-release channels. Despite the individual genetic variabilities, distinct mechanisms have been demonstrated to improve physical performance, thermogenesis, lipolysis, insulin sensitivity, and hormonal modulation. Thus, coffee consumption and caffeine supplementation may enhance physical and mental performance and may improve metabolic variables, reducing oxidative stress, inflammation, and insulin resistance. Current data reveal vital aspects of coffee and caffeine consumption in specific populations, although further studies are needed to define clinical interventions with caffeine in obesity and chronic conditions.