Risk taking can lead to ruin, but sometimes, it can also provide great success. How does our brain make a decision on whether to take a risk or to play it safe? Recent studies have revealed the neural basis of risky decision making. In this review, we focus on the role of the anterior insular cortex (AIC) in risky decision making. Although human imaging studies have shown activations of the AIC in various gambling tasks, the causal involvement of the AIC in risky decision making was still unclear. Recently, we demonstrated a causality of the AIC in risky decision making by using a pharmacological approach in behaving rats-temporary inactivation of the AIC decreased the risk preference in gambling tasks, whereas temporary inactivation of the adjacent orbitofrontal cortex (OFC) increased the risk preference. The latter finding is consistent with a previous finding that patients with damage to the OFC take abnormally risky decisions in the Iowa gambling task. On the basis of these observations, we hypothesize that the intact AIC promotes risk-seeking behavior, and that the AIC and OFC are crucial for balancing the opposing motives of whether to take a risk or avoid it. However, the functional relationship between the AIC and OFC remains unclear. Future combinations of inactivation and electrophysiological studies may promote further understanding of risky decision making.