​The department was originally established as the Department of of Biochemistry by Haim Ernst Wertheimer and Benjamin Shapiro, who in the 1940’s initiated a study on the physiological role of adipose tissue (fat storage tissue). Collectively, these studies established the concept that adipose tissue should be regarded as a dynamic tissue with special physiological functions and considerable biochemical activity, and not merely as an ordinary connective tissue or as an inert site of fat storage. These seminal observations laid the ground for thousands of scientific publications, from all over the world with both biological and clinical implications. Not surprisingly therefore, Shapiro and Wertheimer were both awarded the Israel Prize (1955 and 1956, respectively).

The joining of Shimon Gatt to the department in the late fifties marked a turning point in the department’s scientific interests, from being devoted solely to adipose tissue research to covering a broad range of diverse biological processes. The studies conducted thereafter varied from the molecular level in subcellular compartments, through the level of single cells to multicellular tissues in mammals. These included the research in the following areas: The pathology of lipid storage diseases (Shimon Gatt, 1958); The biochemistry and biophysics of membrane lipids and their relation to the aging process, as well as harnessing this knowledge to the design of liposome-based drug carriers (Yechezkel Barnholz, 1971); The establishment of the glyceroneogenic pathway and the regulation of the key gluconeogenic enzyme at the transcriptional level (Lea Reshef. 1968); The structural basis of the Na+-Ca2+ exchanger (Hannah Rahamimoff, 1975); The molecular mechanism of neurotransmitter transport via membranes (Baruch Kanner, 1976); The regulation of the expression of mammalian house-keeping genes at the translational level (Oded Meyuhas, 1979); The role of extracellular hydrodynamics in cell-membrane function and regulation of inflammatory processes (Saul Yedgar, 1981) and the molecular mechanisms involved in mast cell activity and the implications for allergy (Ehud Razin, 1982).

With the foundation of the Institute for Medical Research, Israel-Canada (IMRIC) at 2009 few additional staff members joined the department and its name was changed to the Department of Biochemistry and Molecular Biology.