Protocol renal allograft biopsies allow the early detection of histological damage in the renal allograft even before renal function deterioration or proteinuria appears. Two different lesions have attracted the main interest in protocol biopsy studies: subclinical rejection, namely, the presence of tubulo-interstitial inflammation and chronic allograft nephropathy, nowadays termed interstitial fibrosis/tubular atrophy (IF/TA), and the presence of tubulo-interstitial chronic lesions. The incidence of subclinical rejection is maximal after transplantation and decreases during the first few months despite the fact that this condition persists in a proportion of cases even in late protocol biopsies done after the first year. In studies of serial protocol biopsies, the presence of subclinical rejection is associated with a higher probability of the progression of chronic tubulo-interstitial lesions and, recently, it has been shown the subclinical rejection in early protocol biopsies is associated with poorer allograft survival. The incidence of IF/TA rapidly progresses after renal transplantation, following an exponential curve. Its presence is associated with a decreased graft survival and its predictive value on outcome is independent from other predictors of survival such as serum creatinine or acute rejection. The association of IF/TA with transplant vasculopathy, subclinical rejection or transplant glomerulopathy implies a poorer outcome than IF/TA without other histological lesions. Taken together, these data suggest that protocol biopsies allow the early detection of acute and chronic lesions and the recognition of different patterns of damage that are associated with allograft survival.