Effective delivery of drugs via liposomes in the treatment or prevention of disease is the aim of numerous researchers worldwide. Therapies include those for cancer, microbial infections, hormone and enzyme deficiencies, metal detoxification, gene deficiency or malfunction, as well as vaccines. Intimate knowledge of the structure and physical properties of liposomes, and of ways such properties influence their behaviour within the biological milieu, is central to their success. The discovery of liposomes in the mid-1960’s [1] and their similarity to cell membranes presented cell biologists with a unique tool for the study of a number of cell membrane functions including cell fusion, membrane pumps and antigen presentation. However, it was not until several years later that liposomes were considered as a candidate carrier for the delivery of pharmacologically active agents in the treatment of disease [2–4].

The use of liposomes in drug delivery and targeting is often discussed in the context of decades marked by significant milestones. Thus, the 1970s are noted for the initial understanding of the system’s behaviour in vivo, namely its interaction with the biological milieu in the living animal and, as a result, the proposition of an array of therapeutic applications. Following a period of “disillusionment” of those (mainly in industry) with expectations unjustified by the degree to which liposomes had been developed at that time, the 1980s were a period of reflection and consolidation. This was also a period of advancements in improving liposomal stability in biological fluids such as blood [5], in liposome technology [6] in terms of developing techniques for high yield entrapment, and the preservation of intact liposomes under storage. Importantly, the founding in 1981 of three liposome-based companies in the USA ensured a systematic transition of some of the earlier concepts [7–9] into realistic goals backed by significant progress in large-scale technology. The 1990s were clearly the decade of clinical trials, approved injectable products (eg, AmBisome, Doxil), and of new horizons. Forty six years after work on the use of liposomes in drug delivery commenced, enthusiasm is still prevailing. The old guard of liposomologists who were ‘there’from the very beginning, but are gradually retiring into new pastures, are being replaced by worthy successors. Below I discuss early developments which are thought to have helped shape the future of the field. My audience includes young liposomologists entrapped in the maze of a myriad of publications of varying clarity, insight, accuracy and, perhaps, bias. My involvement with liposomes, described in more detail elsewhere [10] began with a chance event. In 1969, while in New York, I came across a Nature advertisement for a research post with the late Brenda Ryman (Figure 1) on the delivery of enzymes to the hepatic parenchymal cells. I was attracted by it because of my work [11, 12] at the Albert Einstein College of Medicine, on the discovery of the hepatic galactose receptor and the opportunity presented by the post to pursue galactose-terminating ligands in targeting drugs to the liver. On arrival in Ryman’s laboratory in the summer of 1970, it turned out that one of the candidate systems for enzyme delivery was one called “liposomes”. Other systems also considered were nylon micro capsules and solid support systems. It was obvious, however, even in those early days, that the expected, innocuous, non-toxic biodegradable nature of liposomes, their sub-micrometre size and apparent structural versatility rendered them the candidate of choice. Because of my familiarity with animal work in previous years on the fate of …