Nonsyndromic cleft lip and palate (CL/P) is a common craniofacial malformation with a complex genetic component. Attempts at identifying susceptibility loci via family and case-control studies have proved inconsistent. It is likely that initial predictions of the complex interactions involved in facial development were underestimated. The candidate gene list for CL/P is getting longer and the need for an impartial, systematic screening technique, to implicate or refute the inclusion of particular loci, is apparent. Large-scale multi-centre collaborations will also be necessary if we are to pursue the avenues of gene-environment interactions, which have opened up over recent years. So we are faced with the question ‘Can this complex trait be too complex?’