Carbon monoxide-releasing molecules (CORMs) are promising candidates for producing carbon monoxide in the mammalian body for therapeutic purposes. At higher concentrations, CO has a harmful effect on the mammalian organism. However, lower doses at a controlled rate can provide cellular signaling for mandatory pharmacokinetic and pathological activities. To date, exploring the therapeutic implications of CO dose as a prodrug has attracted much attention due to its therapeutic significance. There are two different methods of CO insertion, i.e., indirect and direct exogenous insertion. Indirect exogenous insertion of CO suggests an advantage of reduced toxicity over direct exogenous insertion. For indirect exogenous insertion, researchers are facing the issue of tissue selectivity. To solve this issue, developers have considered the newly produced CORMs. Herein, metal carbonyl complexes (MCCs) are covalently linked with CO molecules to produce different CORMs such as CORM-1, CORM-2, and CORM-3, etc. All these CORMs required exogenous CO insertion to achieve the therapeutic targets at the optimized rate under peculiar conditions or/and triggering. Meanwhile, the metal residue was generated from i-CORMs, which can propagate toxicity. Herein, we explain CO administration, water-soluble CORMs, tissue accumulation, and cytotoxicity of depleted CORMs and the kinetic profile of CO release.

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