Sub nanometer transition metal clusters composed of a small number of atoms exhibit unexpected electronic, optical, magnetic and catalytic properties that often change substantially as a function of cluster atomicity. Several factors influence their unique catalytic behavior, including their discrete electronic structure of molecular-like orbitals and the accessibility of their low-coordinated atoms. In addition, these factors are strongly correlated so that changes in their morphology may provoke large modifications to their electronic structure and vice versa. The thermodynamic instability of clusters makes it necessary to stabilize them with protective ligands in solution or to support them on solid matrices for practical applications, which introduces non-negligible modifications into their properties. Understanding their cause and extent is the key point to potentially achieve a fine tuning of their catalytic behavior. Selected examples are discussed illustrating important points on this matter, such as the influence of cluster morphology on reactivity, the need of anchoring clusters to avoid sintering and deactivation, and the possible formation of clusters in solution or under reaction conditions, with the associated difficulty to identify them as the true active species.