Compelling evidence now unequivocally demonstrates that platelets play a crucial role as both immune sensors and effectors in innate and adaptive immunity. They contribute both to host defense against bacteria, viruses, parasites and fungi, and to the development of various infectious, inflammatory, and autoimmune diseases. Thus, platelets are the most abundant circulating blood cell type (150–400,000/μL) with an immune function. Connective tissue disorders (CTDs) are a heterogeneous group of chronic, multisystemic, inflammatory, and autoimmune diseases that predominantly impact connective tissue across multiple organs. They arise when the immune system mistakenly targets the body’s own tissues, either through autoantibodies binding to self-antigens to form immune complexes (ICs), or through T cells attacking self-antigens. This dysregulated immune response results in tissue damage and potential organ failure. In addition, CTDs are associated with an increased risk of cardiovascular and thrombotic events. Several observations reported circulating platelet activation in CTDs, as well as their direct involvement in the inflamed tissue. All these observations demonstrate an active role of platelets both in the pathogenesis of CTDs and in the CTD-related increased cardiovascular and thrombotic risk, highlighting the potential role of platelets both as a marker of CTD severity and as a therapeutic target. This chapter focuses on the role of platelets in the pathogenesis of autoimmune connective tissue disorders, including antiphospholipid syndrome (APS), rheumatoid arthritis (RA), Sjögren’s syndrome (SS), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and systemic vasculitis (SV).