The increasing interest in complementary and alternative medicines (CAMs) for musculoskeletal care has sparked significant debate, particularly regarding their biological plausibility and clinical effectiveness. This comprehensive review critically examines the use of two of the most widely utilized CAMs-osteopathy and chiropractic care-over the past 25 years, focusing on their biological plausibility, clinical effectiveness, and potential mechanisms of action. Our analysis of current research and clinical studies reveals that osteopathy and chiropractic are based on concepts such as "somatic dysfunction" and "vertebral subluxation", which lack robust empirical validation. While these therapies are often presented as credible treatment options, studies evaluating their effectiveness frequently exhibit serious methodological flaws, providing insufficient empirical support for their recommendation as first-line treatments for musculoskeletal conditions. The effects and mechanisms underlying osteopathy and chiropractic remain poorly understood. However, placebo responses-mediated by the interaction of contextual, psychological, and non-specific factors-appear to play a significant role in observed outcomes. The integration of therapies with limited biological plausibility, whose effects may primarily rely on placebo effects, into healthcare systems raises important ethical dilemmas. This review highlights the need for rigorous adherence to scientific principles and calls for a more comprehensive investigation into biobehavioral, contextual, and psychosocial factors that interact with the specific effects of these interventions. Such efforts are essential to advancing our understanding of CAMs, enhancing clinical decision-making, promoting ethical practices, and guiding future research aimed at improving patient care in musculoskeletal disorders.