Botrytis bunch rot of grapes is mainly controlled by applying fungicides at three crop growth stages: the end of flowering (BBCH 68), bunch closure (BBCH 77) and the beginning of veraison (BBCH 81). The hydroxyanilide derivative fenhexamid is among the most effective fungicides registered to control Botrytis cinerea. Its effectiveness was examined in relation to spray timing, fungicide resistance and defense responses of grapevine. Overall, the earlier fenhexamid was applied, the more effective it was at controlling B. cinerea. Frequencies of B. cinerea strains which were resistant to fungicides were evaluated at harvest. The frequencies of resistant phenotypes were similar among treatments and years with the exception of a class of multidrug resistant strain (MDR 2) whose frequency appeared to increase after fenhexamid applications. If current spray programs including fenhexamid appear to control bunch rot at the current MDR frequency, a propagation of MDR 2 strains might lead to a decline in disease control. Finally, defense responses were studied in grapevine flowers/berries following fenhexamid application. None of the defense processes tested was induced in flowers/berries at stages 68 and 77. Only an increase in chitinase activity was observed in treated-berries at stage 81, suggesting that fenhexamid effectiveness was not related to a stimulation of defense responses.