Healing process might be considered as a byproduct of the mechanisms underlying the biological defense system consisting of hemostasis and clotting, the innate immune system, and fibrogenesis. But there is no biological process that does not potentially entail high costs through trade-offs with other life-history parameters and that might be seen as collateral damage. Depending on the balance among the robust and flexible modular defense system, which will be deployed in many different arrays, the structural outcome of the healing process will not resolve with a unitary outcome. Drawing on the regenerative potential of platelets, plasma biomolecules and fibrin matrix, several systems of producing autologous platelets-and plasma derived products (APPDPs) have been developed and aimed at enhancing the natural in vivo tissue regenerative capacity of damaged tissues. Despite the care with which the medical staff elaborate and apply autologous platelets-and plasma derived products, some pitfalls arise regarding the composition of autologous plasma-and platelet derived products, the modalities of their application, and the in vitro versus in vivo evaluations, all of which can deeply influence tissue healing – a process which is already unpredictable, without a unitary mechanism that might be deployed in many different structural and functional arrays which culminate in the tissue repair. A biological approach to the application of autologous platelets-and plasma derived products is crucial to obtaining optimum functional healing outcomes in addition to avoiding poor clinical results and reaching misleading conclusions.