Owing to the overall increase in the use of DES, the number of patients presenting with DES restenosis is not insignificant in absolute terms. When DES restenosis occurs, it represents a challenging clinical entity in terms of classification and treatment. By providing near histology-level images, intravascular optical coherence tomography (OCT) has been used to describe vascular responses following PCI. Subsequently, OCT has been introduced to assess neointimal morphology and tissue characteristics of restenotic lesions to clarify the underlying pathophysiology. OCT imaging is best suited to reflect morphological characteristics of restenotic lesions, where its application enables to provide quantitative measures of neointimal growth and, more importantly, differentiate qualitative tissue properties amenable to specific treatment algorithms. Finally, morphological assessment of restenotic lesions might entail dedicated treatment strategies and accomplish individualized patient-care. Whether the OCT-guided treatment of restenotic lesions might improve outcomes of this challenging clinical entity remains unanswered, since implementation and adequate treatment algorithms are matter of current debate.