There is still no definitive treatment for knee osteoarthritis (OA). We are certainly far from a consensus on the best form of treatment or on an effective treatment recommendation. There are reasons for the current equivocal treatment recommendations in the face of this very serious health problem. The greatest of these reasons, undoubtedly, is the great complexity of the factors involved in the development and progression of knee OA and the complex pathophysiology including mechanical, inflammatory, metabolic, post-traumatic, molecular, genetic, and psychological changes. For several years, an attempt has been made to correlate different patient phenotypes to different patterns of response to treatment, thus creating the possibility of developing specific treatments for certain groups of patients and theoretically allowing better treatment efficacy. However, in practice we still find totally different responses and evolutions even in individuals belonging to the same phenotype. Thus, classification by phenotypes, despite being an advance, is not sufficient. The present article proposes a fragmented look at each of the many factors or targets involved in the genesis and evolution of OA. Therefore, we propose not the treatment of OA per se but the management of an individual set of targets to achieve personalized OA management. We believe that, paradoxically, by fragmenting the view of the disease we will be able to treat our patients more holistically in an individualized way.