DNA is an established biological target for many organic natural products that react by alkylation or H-atom abstraction via key functional groups such as cyclopropane, aziridine, enediyne, and terminal diazo functionalities. Remarkably, although more than 20 natural product derivatives compose the latter class, the precise mechanism of action and specific biological target remain to be elucidated. Despite these biochemical uncertainties, more than 100 years of diazo/diazoketone chemistry exists. Much of this work involves photochemical N2 extrusion to generate an initial carbene intermediate capable of insertion (singlet), H-atom abstraction (triplet), or ketene formation and subsequent nucleophilic addition (Wolff rearrangement). The trigger advantage of photochemical reactivity, coupled with the entropic gain of deazetation, and the high reactivity of the resulting intermediate, have led researchers to consider diazo compounds as potential phototherapeutric agents for medical applications. Such a strategy could serve as an alternative to 1O2 generation in photodynamic therapy (PDT), particularly in solid tumors or other hypoxic environments. Since diazoparaquinone natural products, and diazo compounds in general, are susceptible to redox activated N2 loss, transition metal complexes containing redox-active excited states that absorb in the tissue transparent therapeutic window have potential as new therapeutic agents. Moreover, highly π-conjugated molecules such as porphyrins and chlorins, which serve as the primary pigment for current PDT due to intense absorption bands throughout the region of 600 – 850 nm, have only recently been able to support a conjugated diazoketone functionality at the macrocycle periphery. These synthetic advances have now made diazo activation through visible region photolysis possible, and have led to characterization of a range of remarkable molecular photoproducts including azeteoporphyrinoids and O – H/N – H insertion products. In addition to protein or DNA alkylation, the latter reactivity leads to potential for these constructs to serve as in situ biological labels or as recognition elements to probe biochemical mechanisms.