This review article proposes a non-covalent strategy for activating separation and detection functionality; this strategy acts not through extensive organic synthesis to a covalently constructed molecular receptor, but by combining a simple molecular platform with a chemical “field” or functional component. For such a platform, we employed thiacalixarenes—calixarenes in which the bridging methylene groups are replaced with sulfur—to demonstrate usefulness of the non-covalent strategy and the multifunctionality of thiacalixarene. Thiacalixarene exhibits inherent abilities to recognize metal ions by coordinating with the bridging sulfur and adjacent phenol oxygen, as well as to include organic guest molecules in the cavity. Moreover, the non-covalent coupling of thiacalixarene provides systems with functions higher than thiacalixarene by itself. The functions described in this paper are as follows: (1) a 200-fold pre-concentration of heavy metal ions such as CuII, CdII, and PbII; (2) a pre-column derivatization reagent for the highly selective and sensitive determination of NiII, AlIII, FeIII, and TiIV at sub-ppb levels with reversed-phase HPLC; (3) the self-assembled formation of a luminescence receptor with TbIII ions for the detection of 10−10 M levels of 1-ethylquinolinium guest; and (4) a sensing system for 10−9 M levels of AgI ions by the formation of the AgI-TbIII-thiacalixarene ternary supramolecular complex. These examples support the non-covalent strategy as a highly promising way to obtain functions beyond that of a molecular platform. In addition, these diverse functions indicate the multifunctionality of thiacalixarene as well as its suitability to the non-covalent strategy, since the inherent functional groups—such as the bridging sulfur, phenol oxygen, p-substituent, aromatic ring, and hydrophobic cavity—synergistically perform the functions.