Recent preclinical and clinical evidence using prazosin indicates that α1-blockade may represent a new approach to treat alcohol dependence (AD). While most of the alcohol research on α1-blockade has been conducted testing prazosin, O'Neil and colleagues recently performed a set of preclinical experiments testing another α1-blocker, doxazosin, which has a longer half-life that may enhance clinical utility. Doxazosin and prazosin share the same chemical structure, in which the central element is a piperazine ring. O'Neil and colleagues' main results are that doxazosin significantly reduced alcohol intake without affecting locomotor activity. As such, O'Neil and colleagues provide the first preclinical evidence of the possible role of doxazosin in AD. Additional translational research is needed to further test this hypothesis.