The treatment of degenerative diseases such as osteoarthritis remains one of the key challenges in modern medicine. The rising prevalence of this condition, driven by increased life expectancy and demographic changes, underscores the urgent need for innovative, minimally invasive therapeutic approaches. Regenerative therapies, particularly those utilizing adipose-derived stem cell (ADSC) techniques, offer promising prospects. ADSC therapies can improve patients’ quality of life through anti-inflammatory effects. Autologous fat transplantation gained attention within the last decade in many different applications, particularly in hand surgery for the treatment of thumb carpometacarpal (CMC) osteoarthritis. Over the past 5 years, studies with extended follow-up periods have increasingly demonstrated the sustained efficacy of this approach. Meta-analyses confirm that autologous fat transplantation provides long-lasting symptom relief. Despite these advances, the precise mechanisms of ADSC activity within the arthritic environment remain incompletely understood, representing a critical focus for basic research in this field. This chapter provides an overview of the current state of research on autologous fat transfer for osteoarthritis of the thumb and a clinical approach to how to perform in your clinic.