Research has so far failed to explain why entrepreneurs bear a high level of stress but do not withdraw from the pursuit of opportunity. We conducted a pharmaceutical study including 120 nascent entrepreneurs and control participants. We theorize that higher levels of dopamine and noradrenaline compensate for the otherwise negative effects of the stress hormone, cortisol, on optimism and the propensity for risk, which are the key factors in the pursuit of opportunity. Our findings support the idea that entrepreneurs develop differences in neurotransmitter receptors by showing that increased dopaminergic and noradrenergic activity compensates for the negative effects of stress.