The term “sarcopenia” describes the progressive decline of muscle mass, strength and function occurring with aging. It is not considered a disease, but the direct consequence of the aging process on the skeletal muscle. Multiple demographic (e.g. gender, race), biological (e.g. inflammatory status) and clinical (e.g. diabetes, metabolic syndrome, congestive heart failure, medications) factors are able to influence (positively or negatively) the skeletal muscle quality and quantity. The extreme paucity of clinical trials on sarcopenia in literature is mainly due to difficulties in designing studies able to isolate the aging process from its multiple and interconnected consequences. In the present review, we present the major factors to consider as potential sources of biased results when evaluating potential candidates for clinical trials on sarcopenia. The development of clinical trials exploring the nature of the sarcopenia process is urgent, but several controversial issues on this hallmark of aging still need clarification.