The largely unanticipated difficulties of parasite vaccine development have led us to a renewed awareness of the survival strategies evolutionarily embedded within parasites over hundreds of millions of years. We have grown to appreciate that efforts to disrupt parasite–host relationships are substantially compounded by our incomplete understanding of the complex immune responses that occur in the naturally infected host. Given the inability to transfer laboratory successes to field trials, research is leading us to conclude that genetically defined animal models may not be good predictors of the unique and disparate protective immune responses one can expect from the genetically heterogeneous populations of animals that represent the parasite's natural environment. This is further compounded by the abundance of mechanisms parasites have created for themselves to defend against immune intervention. Thus, in the never-ending saga of vaccine development, it is only appropriate that pitfalls and advancements be critiqued as they apply across parasite groups, with a look towards promising technologies that may propel this field to the level of scientific achievement once envisaged.