Patellofemoral cartilage disease—from focal defects to osteoarthritis—is a major cause of anterior knee pain and disability. Prevalence is high in community and symptomatic cohorts; lesions are frequent in athletes and arthroscopy series. The joint’s anatomy and variable high loads drive multifactorial pathology, often with malalignment or instability. This chapter reviews biologic strategies for patellofemoral disease, focusing on injectables and cell-based options. Platelet-rich plasma (PRP) provides greater symptomatic improvement than hyaluronic acid and more durable benefit than corticosteroids; multi-dose regimens outperform single injections. Appropriateness criteria support PRP for Kellgren–Lawrence 0–III after failed conservative care and discourage use in grade IV or as first-line therapy. Cell-based approaches—including bone marrow aspirate concentrate and adipose-derived products—show encouraging mid-term outcomes in selected patients, especially when combined with biomechanical optimization and rehabilitation. A stepwise, patient-centered pathway with standardized product characterization and PFJ-specific outcomes is recommended.