Nucleic acids, phospholipids and other organic phosphates play central roles in biological pathways. n-Alkyl phosphates and their derivatives have been recognized as amphiphilic molecules for nearly two centuries. In the last 50 years, n-alkyl phosphate derivatives such as di-alkyl phosphates, mono-alkyl phosphatidyl ethanol amines and mono-alkyl phosphocholines have become predominant compounds with applications in different areas, from food chemistry to life science. The aim of this review is to summarize the most relevant progress made in the field of the synthesis of these molecules and to provide a concise perspective on the use of these amphiphiles as possible prebiotic membrane constituents. The first part of the review is dedicated to the analysis of the most relevant syntheses carried out in recent years with respect to those reported from the second half of the nineteenth century. The second part is dedicated to a description of the latest reports on prebiotic synthesis of mono-alkyl phosphates. In this part, the authors did not report the phosphorylation of other relevant biomolecules, such as nucleosides, which have been excellently reviewed elsewere.