Random noise applied to the end caps of a quadrupole ion trap is shown to be an effective means for the collisional activation of trapped ions independent of mass/charge ratio and number of ions. This technique is compared and contrasted with conventional single-frequency collisional activation for the molecular ion of N,N-dimethylaniline, protonated cocaine, the molecular anion of 2,4,6-trinitrotoluene, and doubly pronated neuromedin U-8. Collisional activation with noise tends to produce more extensive fragmentation than the conventional approach due to the fact that product ions are also kinetically excited in the noise experiment. The efficiency of the noise experiment in producing detectable product ions relative to the conventional approach ranges from being equivalent to being a factor of 3 less efficient. Furthermore, discrimination against low mass/charge product ions is apparent in the data from multiply charged biomolecules. Nevertheless, collisional activation with random noise provides a very simple means for overcoming problems associated with the dependence of single-frequency collisional activation on mass/charge ratio and the number of ions in the ion trap.