An overview of the chemistry of isoporphyrin, the tautomer of porphyrin, whose existence was predicated by the Noble laureate Woodward, is presented with emphasis on hydroxy-isoporphyrins of tetra-aryl derivatives. The chemistry of metalloisoporphyrin has been discussed since the discovery of the first metallo-isoporphyrin by Dolphin and co-workers, as no comprehensive article is available on this beautiful macrocycle. Attention is paid to the possible applications of metalloisoporphyrins as photosensitizers in photodynamic therapy, as a near infra-red dye and as a reactive agent for different atom transfer reactions. Some important findings about reactivity and theoretical results of hydroxy-isoporphyrins are discussed. Furthermore, the approaches of heme oxidation via isoporphyrin as an intermediate to understand the heme oxygenase mechanism are discussed. The metalloisoporphyrins are discussed reviewing coordination modes, structural changes, electronic properties and biological relevance.