The underlying background and present development of methanol tolerant electrocatalysts, selective for the oxygen reduction reaction (ORR), are presented. These catalysts are essentially metal‐centered (ruthenium) clusters or cluster‐like compounds. These clusters, partially embedded in a chalcogenide matrix (e.g., selenium) constitute the active center for the electrochemical process ORR. On well‐defined cluster materials, as for example, the so‐called Chevrel phases, based on octahedron clusters [(Mo
2/3
Ru
1/3
)
6
Se
8
], the ORR electrochemical activity clearly indicated that this phenomenon can be selectively sustained with a four‐electron charge transfer (water formation). This is due to their electronic and geometric characteristics. Hence, clusters work as a pool of charges that can be engaged in a multi‐electron process. Therefore, this family of materials served as a model for the development of novel ones. In this respect, e.g., Ru
x
Se
y
(
x
≈ 2,
y
≈ 1), tailored from chemical precursors in organic solvents, under mild conditions, shows a high dispersiveness in the nanoscale range. The metallic center shows similar electrochemical properties to those of well‐defined Chevrel phases, thus behaving as a cluster‐like material. The ability of the catalytic center to provide coordination chemistry for reactivity and selectivity via cluster, or cluster‐like compounds is discussed, as well as the trends in the synthesis and the results of tests in half‐cells and in direct methanol fuel cell systems.