Protein kinase C (PKC) is a central enzyme that modulates numerous biological functions. For this reason, specific PKC inhibitors/activators are required to study PKC-related signaling mechanisms. To date, although many PKC inhibitors have been developed, they are limited by poor selectivity and nonspecificity. In this review, we focus on the nonspecific actions of PKC inhibitors on cardiovascular ion channels in addition to their PKC-inhibiting functions. The aim of this paper is to urge caution when using PKC inhibitors to block PKC function. This information may help to better understand PKC-related physiological/biochemical studies.