The frequency of suppressing translation termination codons in S. cerevisiae can be increased several hundred fold by altering the local sequence context surrounding termination codons. This process appears to be mediated by near-cognate tRNA mispairing with the stop codon. We have now examined how distinct features of the local sequence context act to alter the efficiency of translation termination in yeast. It appears that upstream and downsteam components of an extended translation termination signal act in a synergistic manner to determine the overall efficiency of translation termination. In particular, a tetranucleotide termination sequence (containing the stop codon and the first distal nucleotide) functions as an important determinant of termination efficiency. As previously reported by others, we also found that low levels of certain aminoglycoside antibiotics can increase the readthrough of stop codons by as much as 20 fold. Some aminoglycosides induced readthrough in a context-specific manner, while others showed the ability to induce readthrough in all contexts examined. We recently extended this analysis to stop mutations in human cells. We found that certain aminoglycosides can induce the suppression of premature stop mutations in the human CFTR gene, suggesting that this may provide a pharmacological approach to treating human diseases caused by premature stop mutations.