Nickel contents of olivine have been widely used as petrogenetic indicators and as fertility indicators for magmatic sulfide potential of mafic-ultramafic intrusions, on the assumption that olivines crystallized from magmas that had equilibrated with sulfide liquid should be relatively depleted in Ni compared with a sulfide-free baseline. This has given rise to a large accumulation of data that is brought together here, along with data on volcanic olivines, to critically evaluate the effectiveness of the approach. We identify multiple sources of variance in Ni content of olivine at a given Fo content, including variability in mantle melt composition due to depth, water content (and possibly source), subsequent fractional crystallization with and without sulfide, recharge and magma mixing, batch equilibration between olivine and sulfide at variable silicate-sulfide ratio (R), and olivine/liquid ratio; and subsequent equilibration during trapped liquid crystallization in orthocumulates. Baselines for Ni in olivine in relation to Fo content are somewhat lower in orogenic belt settings relative to intrusions in continental large igneous provinces (LIPs). This is probably related to differences in initial parent magma compositions, with plume magmas generally forming deeper and at higher temperatures. No clear, universal discrimination is evident in Ni in olivine between ore-bearing, weakly mineralized, and barren intrusions, even when tectonic setting is taken into account. However, sulfide-related signals can be identified at the intrusion scale in many cases. Low-R factor and low-tenor sulfides are associated with low-Ni olivines in several examples, and these cases stand out clearly. Anomalously high-Ni olivines are a feature of some mineralized intrusions, in part due to trapped liquid reaction effects. However, in some cases, this mechanism cannot account for the magnitude of enrichment. In these cases, enrichment may be due to re-entrainment of “primitive” Ni-rich sulfide by a more evolved Fe-rich magma, driving the olivine to become Ni-enriched due to Fe-Ni exchange reaction between sulfide and olivine during transport. An extreme case of this process may account for ultra-Ni enriched olivine at Kevitsa (Finland), but more subtle signals elsewhere could be positive indicators. A lack of clear mineralized/barren distinction in specific groups of related intrusions, e.g., the deposits of NW China or the Kotalahti Belt in Finland, may well be due to “false negatives” where undiscovered mineralization exists in specific intrusions or in their feeder systems, or may also be due to a multiplicity of confounding factors. Wide variability of both Fo and Ni between related intrusions at regional scale may be a useful regional prospectivity indicator, more than an intrusion-scale discriminant, and is certainly informative as a petrogenetic indicator. In general, the use of Ni-olivine as a fertility tool is more likely to generate false negatives than false positives, but both are possible, and the technique should be used as part of a broader weight-of-evidence approach.