Combination of photodynamic therapy (PDT) with other treatment modalities is emerging as one of the most suited strategy to increase the effectiveness of the therapeutic action on cancer and bacterial diseases and to minimize side effects. In view of the key role nitric oxide (NO) plays in cancer and bacterial diseases, the coupling of PDT with photocontrolled release of nitric oxide (NO) through the appropriate assembling of PDT photosensitizers (PSs) and NO photodonors (NOPDs) may open intriguing horizons towards new and still underexplored multimodal therapies not based on “conventional” drugs and entirely controlled by light stimuli. In this contribution, we present an overview of the most recent advances in this field, illustrating several strategies to assemble PSs and NOPDs allowing them to operate independently without reciprocal interferences and describing the potential applications with particular emphasis to their impact in anticancer and antibacterial research.