Phytophthora infestans, a hemibiotrophic and heterothallic oomycete pathogen, attacks a wide variety of crop plants belonging to the Solanaceae family. In 2007, late blight symptoms were observed and confirmed on Physalis peruviana in fields during a late blight survey in Colombia. Subsequent to these observations, no further symptoms have been detected in the field. This prompted an interest in investigating the interaction between P. infestans and P. peruviana using histological and molecular assays, as well as characterizing defence reactions produced on P. peruviana leaves. During this interaction, callose depositions, accumulation of hydrogen peroxide, activation of pathogenesis-related proteins (β-1,3 glucanase and peroxidase), induction of the expression of genes associated with plant defences (glucanase A and carbonic anhydrase) as well as cell death, showed that P. peruviana has active defences against P. infestans strains present in Colombia.