Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease, and it leads to end-stage renal disease (ESRD). The clinical manifestations of ADPKD are variable, with extreme differences observable in its progression, even among members of the same family with the same genetic mutation. In an age of new therapeutic options, it is important to identify patients with rapidly progressive evolution and the risk factors involved in the disease’s poor prognosis. As the pathophysiological mechanisms of the formation and growth of renal cysts have been clarified, new treatment options have been proposed to slow the progression to end-stage renal disease. Furthermore, in addition to the conventional factors (PKD1 mutation, hypertension, proteinuria, total kidney volume), increasing numbers of studies have recently identified new serum and urinary biomarkers of the disease’s progression, which are cheaper and more easily to dosing from the early stages of the disease. The present review discusses the utility of new biomarkers in the monitoring of the progress of ADPKD and their roles in new therapeutic approaches.