The microtubule-system organizes the cytoplasm during interphase and segregates condensed chromosomes during mitosis. Four unrelated conserved proteins, XMAP215/Dis1/TOGp, MCAK, MAP4 and Op18/stathmin, have all been implicated as predominant regulators of tubulin monomer-polymer partitioning in animal cells. However, while studies employing the Xenopus egg extract model system indicate that the partitioning is largely governed by the counteractive activities of XMAP215 and MCAK, studies of human cell lines indicate that MAP4 and Op18 are the predominant regulators of the interphase microtubule-array. Here, we review functional interplay of these proteins during interphase and mitosis in various cell model systems. We also review the evidence that MAP4 and Op18 have interphase-specific, counteractive and phosphorylation-inactivated activities that govern tubulin subunit partitioning in many mammalian cell types. Finally, we discuss evidence indicating that partitioning regulation by MAP4 and Op18 may be of significance to establish cell polarity.