Abstract Fouling is a key issue which limits the practical applications of electrochemical sensors (ECSens) in both in vitro and in vivo analysis. The analytical sensitivity, limit of detection (LOD), selectivity, reproducibility and life‐time of ECSens are all greatly affected by fouling. Although numerous methods and materials have been developed to minimize the fouling effect in past several decades, not all of them are suitable for constructing antifouling ECSens. In this paper we present an overview of surface antifouling strategies for ECSens. We begin with a short summary of sources and impacts of fouling under both in vitro and in vivo environments. Then the current surface antifouling strategies for ECSens are discussed, including self‐assembled monolayers (SAMs), antifouling polymers, porous coating, in‐situ electrochemical and photocatalytic cleaning. The antifouling mechanisms, advantages and challenges of each strategy are briefly summarized. The article ends up with a short conclusion and perspectives. We hope this article is helpful for constructing and designing ECSens with both outstanding antifouling performance and electrochemical activity for electrochemical analysis.