Methanol cross-over effects from the anode to the cathode are important parameters for reducing catalytic performance in direct methanol fuel cells. A promising candidate catalyst for the cathode in direct methanol fuel cells must have excellent activity toward oxygen reduction reaction and resistance to methanol oxidation reaction. This review focuses on the methanol tolerant noble metal-based electrocatalysts, including platinum and palladium-based alloys, noble metal-carbon based composites, transition metal-based catalysts, carbon-based metal catalysts, and metal-free catalysts. The understanding of the correlation between the activity and the synthesis method, electrolyte environment and stability issues are highlighted. For the transition metal-based catalyst, their activity, stability and methanol tolerance in direct methanol fuel cells and comparisons with those of platinum are particularly discussed. Finally, strategies to enhance the methanol tolerance and hinder the generation of mixed potential in direct methanol fuel cells are also presented. This review provides a perspective for future developments for the scientist in selecting suitable methanol tolerate catalyst for oxygen reduction reaction and designing high-performance practical direct methanol fuel cells.