There is a global unmet need for autologous non-surgical tissue repair strategies to treat a magnitude of musculoskeletal disorders (MSK), like osteoarthritis (OA), cartilage defects, tendinopathies, and other soft tissue maladies (Everts PA, Mazzola T, Mautner K, Randelli PS, Podesta L, Biomedicines 10:2933, 2022). Autologous biological cellular preparations have materialized as a growing area of medical advancement in interventional (orthopedic, pain management) practices and surgical interventions to initiate tissue repair, particularly in tissues where standard healing is disrupted, and the restoration of function is at risk (Ramires LC, Jeyaraman M, Muthu S, Shankar AN, Santos, GS, da Fonseca LF, Lana JF, Rajendran RL, Gangadaran P, Jogalekar MP, Cardoso AA, Life 12:399, 2022). These cellular therapies, referred to as orthobiologics, are different biological materials comprised of a wide variety of cell populations, growth factors, cytokines, biomolecules, and signaling cells (Everts PA, Flanagan G, Podesta L, Clinical guide to musculoskeletal medicine: a multidisciplinary approach. Springer International Publishing, Cham, 2022). They can be derived from patient’s own tissues, like peripheral blood, bone marrow, and adipose tissue. In this chapter, we discuss solely the applications of platelet-rich plasma (PRP), and focus on PRP formulations, with emphasis on platelet dosing and the importance of integrating leukocytes into the PRP composition, as platelet dosage and bioformulation affect tissue repair, regeneration, and wound healing. Additionally, we discuss the importance of optimal PRP preparation methods, because high concentrations of multiple PRP constituents have the potential to modulate and influence a wide range of other tissue-resident cells depending on the pathoanatomic microenvironment (Oh JH, Kim W, Park KU, Roh YH, Am J Sports Med 43:3062–70, 2015). The literature indicates that PRP applications, with a proper platelet dose and bioformulation, precisely delivered, will respond to catabolic reactions by provoking an effective immunomodulatory response, facilitate control of inflammation, re-establish angiogenesis, and stimulate local cellular synergistic behavior to reinstate tissue homeostasis (Bansal H, Leon J, Pont JL, Wilson DA, St SM, Bansal A et al, Sci Rep 11, 3971; Meizlish ML, Franklin RA, Zhou X, Medzhitov R Annu Rev Immunol 39:557, 2021). The goal of PRP therapies, as well as other orthobiological preparations, is to effectively treat patients in a non-surgical fashion to re-institute functional tissue repair, regeneration, and body movement patterns. The authors hope to convince readers that there is no “one-size-fits-all” PRP solution for treating the many MSK pathologies that may be effectively treated with appropriate PRP formulations. To realistically illustrate the differences between different PRP devices and their preparation methods, we will provide detailed information regarding PRP preparation methods by implementing various biological formulas that can easily be used in treating patients.