Optical control of the primary step of photoisomerization of the retinal molecule in bacteriorhodopsin from the all-trans to the 13-cis state was demonstrated under weak field conditions (where only 1 of 300 retinal molecules absorbs a photon during the excitation cycle) that are relevant to understanding biological processes. By modulating the phases and amplitudes of the spectral components in the photoexcitation pulse, we showed that the absolute quantity of 13-cis retinal formed upon excitation can be enhanced or suppressed by ±20% of the yield observed using a short transform-limited pulse having the same actinic energy. The shaped pulses were shown to be phase-sensitive at intensities too low to access different higher electronic states, and so these pulses apparently steer the isomerization through constructive and destructive interference effects, a mechanism supported by observed signatures of vibrational coherence. These results show that the wave properties of matter can be observed and even manipulated in a system as large and complex as a protein.