An estimated 10% of salmon become infected with Saprolegnia species each year. At present, there is no efficient treatment available, and therefore, saprolegniosis has become an increasing problem worldwide. Vaccine trials have been conducted, exploring a classical and a reverse vaccinology approach, while testing DNA vaccinations as a means of immunization. The DNA vaccination of Atlantic salmon with each of ten mixtures of six genes coding for S. parasitica protein candidates did not show any significant effects in terms of protection. Vaccination with a protein homogenate did not protect against infection either, but it reduced the disease pathology. The trials provided strong evidence that DNA vaccination of Atlantic salmon with S. parasitica genes can drive heterologous gene expression in salmon myocytes and a simple and efficient protocol was developed for detecting proteins in muscle samples.