<p>Originally, whole-body cryotherapy (WBC) was employed as a therapeutic method for alleviating pain associated with various musculoskeletal conditions in sports medicine. In recent years, its application has gained increasing attention across multiple medical fields, particularly in rheumatology, psychiatry, and neurology. WBC appears to exert anti-inflammatory and analgesic effects primarily through the modulation of cytokine activity, leading to pain reduction and improved functional outcomes. Cardiovascular responses are generally well-tolerated in healthy individuals, although contraindications must be carefully assessed. In rheumatologic conditions—especially rheumatoid arthritis and fibromyalgia—WBC has shown efficacy in reducing inflammation and disease activity. Emerging evidence also supports its adjunctive use in the treatment of depression and multiple sclerosis, with observed benefits in mood disorder symptoms, fatigue, and even markers of oxidative stress. While WBC is considered safe when applied under controlled conditions, study findings remain heterogeneous, largely due to variability in treatment protocols and patient populations. The long-term effects of WBC are still insufficiently explored. Future research should focus on standardizing treatment parameters and identifying the patient subgroups most likely to benefit. Overall, WBC shows promise as a complementary intervention in contemporary clinical practice. This review aims to discuss current evidence regarding WBC’s physiological effects, clinical applications, safety profile, and procedural requirements.</p>