The expression or replication of genes is affected by the binding of small molecule ligands and proteins to nucleic acid sequences. Such binding events are critical for the physiological integrity of organisms and therefore are of fundamental interest to life scientists. Recently, the thermodynamics driving these interactions have also become important to pharmaceutical scientists investigating the anticancer, antibacterial and antiviral potential of nucleic acid/ligand interactions. In addition, as the number of diseases identified as being due to a malfunction of cellular control processes increases, the possibility of treating disorders by manipulating gene expression is further focusing attention on the thermodynamics underlying nucleic acid binding affinity and specificity.