We examined a sample of 90 individuals that had previously received a course of appropriate antibiotics for Lyme disease without experiencing full resolution of their symptoms and had evidence of persistent infection documented by PCR analysis. Mean duration of symptoms was 9.5 years (range 1 - 40 years). The treatment was adapted to the individual case according to clinical response. Long term antibiotic therapy was initiated and patients were treated continuously for at least 6 months, in some cases several years of intermittent therapy was administered. About 38.8% of the patients experienced full remission of symptoms while about 56.7% reported a significant improvement, 5.6% of patients were deemed refractory to therapy. Therapeutic modalities are discussed in detail.