The synthesis of modified nucleic acids has been the subject of much study ever since the structure of DNA was elucidated by Watson and Crick at Cambridge and Wilkins and Franklin at King's College over half a century ago. This review describes recent developments in the synthesis and application of these artificial nucleic acids, predominantly the phosphoramidites which allow for easy inclusion into oligonucleotides, and is divided into three separate sections. Firstly, modifications to the base portion will be discussed followed secondly by modifications to the sugar portion. Finally, changes in the type of nucleic acid linker will be discussed in the third section. Peptide Nucleic Acids (PNAs) are not discussed in this review as they represent a separate and large area of nucleic acid mimics.