Background The mechanism by which volatile anesthetics(VAs) modulate protein activity is one of the major challenges facing molecular pharmacology. Accumulating biochemical evidence demonstrates that VAs modula te ion channel functions in an allosteric mode(i.e. perturbation of the gating machinery), as opposed to a competitive mode (i.e. direct interaction with the ligand binding site). Objective To review the allosteric mechanism of VAs action Content The high-resolution crystal structure of the lymphocyte function associated antigen-1 (LFA-1) domain in complex with the VA isoflurane reveals, for the first time, a detailed atomic view of VA binding to the well-established allosteric pocket critical for conformational transition of the integrin between an active and an inactive state. The isoflurane binding site within the LFA-1 domain involves an array of amphiphilic interactions and correlates remarkably well with a postulated “common anesthetic binding motif” observed in model proteins examined by X-ray crystallography. These results suggest that the mechanisms underlying the allosteric modulation of protein function might be generalized to VA-ion channel interactions in the central nervous system(CNS). Trend The allosteric modulation of VAs may be verified by high-resolution crystal structures of these CNS targets bound to VA.