Within the last decade, the first generation of flow injection (FI) has been supplemented by sequential injection (SI), also termed the second generation, and, recently, by the third generation, i.e., SI-Lab-on-Valve (SILOV). As apparent from the literature, FI and/or SI have become dominant as substitutes for labor-intensive, manual, sample-pre-treatment and/or solution-handling procedures prior to analyte detection by inductively coupled plasma mass spectrometry (ICP-MS). The present review presents and discusses the progress of the state of the art in implementing miniaturized FI/SI systems for on-line matrix separation and pre-concentration of trace levels of metals with detection by ICP-MS. It highlights some of the frequently applied on-line, sample-pre-treatment schemes, including solid phase extraction (SPE), on-wall molecular sorption and precipitate/(co)-precipitate retention using a polytetrafluoroethylene (PTFE) knotted reactor (KR), solvent extraction-back extraction and hydride/vapor generation. It also addresses a novel, robust approach, whereby the protocol of SI-LOV-bead injection (BI) on-line separation and pre-concentration of ultra-trace levels of metals by a renewable microcolumn is interfaced to ICP-MS, as conducted in the present authors' group. It discusses the future outlook in this field.