This review summarizes key developments in the heparanase field obtained 20 years prior to cloning of the HPSE gene and nearly 20 years after its cloning. Of the numerous publications and review articles focusing on heparanase, we have selected those that best reflect the progression in the field as well as those we regard important accomplishments with preference to studies performed by scientists and groups that contributed to this book. Apart from a general ‘introduction’ and ‘concluding remarks’, the abstracts of these studies are presented essentially as published along the years. We apologize for not being objective and not being able to include some of the most relevant abstracts and references, due to space limitation. Heparanase research can be divided into two eras. The first, initiated around 1975, dealt with identifying the enzyme, establishing the relevant assay systems and investigating its biological activities and significance in cancer and other pathologies. Studies performed during the first area are briefly introduced in a layman style followed by the relevant abstracts presented chronologically, essentially as appears in PubMed. The second era started in 1999 when the heparanase gene was independently cloned by 4 research groups [1–4]. As expected, cloning of the heparanase gene boosted heparanase research by virtue of the readily available recombinant enzyme, molecular probes, and anti-heparanase antibodies. Studies performed during the second area are briefly introduced followed by selected abstracts of key findings, arranged according to specific topics.