Metal-organic　frameworks　(MOFs)　have　been　attracting　tremendous　attention　owing　to　their　great　structural　diversity　and　functional　tunability.　Despite　numerous　inherent　merits　and　big　progress　in　the　fundamental　research　(synthesizing　new　compounds,　discovering　new　structures,　testing　associated　properties,　etc.),　poor　chemical　stability　of　most　MOFs　severely　hinders　their　involvement　in　practical　applications,　which　is　the　final　goal　for　developing　new　materials.　Therefore,　constructing　new　stable　MOFs　or　stabilizing　extant　labile　MOFs　is　quite　important.　As　with　them,　some　＂potential＂　applications　would　come　true　and　a　lot　of　new　applications　under　harsh　conditions　can　be　explored.　Efficient　strategies　are　being　pursued　to　solve　the　stability　problem　of　MOFs　and　thereby　achieve　and　expand　their　applications.　In　this　Account,　we　summarize　the　research　advance　in　the　design　and　synthesis　of　chemically　stable　MOFs,　particularly　those　stable　in　acidic,　basic,　and　aqueous　systems,　as　well　as　in　the　exploration　of　their　applications　in　several　expanding　fields　of　environment,　energy,　and　food　safety,　which　have　been　dedicated　in　our　lab　over　the　past　decade.　The　strategies　for　accessing　stable　MOFs　can　be　classified　into:　(a)　assembling　high-valent　metals　(hard　acid,　such　as　Zr4+,　Al3+)　with　carboxylate　ligands　(hard　base)　for　acid-stable　MOFs;　(b)　combining　low-valent　metals　(soft　acid,　such　as　Co2+,　Ni2+)　and　azolate　ligands　(soft　base,　such　as　pyrazolate)　for　alkali-resistant　MOFs;　(c)　enhancing　the　connectivity　of　the　building　unit;　(d)　contracting　or　rigidifying　the　ligand;　(e)　increasing　the　hydrophobicity　of　the　framework;　and　(f)　substituting　liable　building　units　with　stable　ones　(such　as　metal　metathesis)　to　obtain　robust　MOFs.　In　addition,　other　factors,　including　the　geometry　and　symmetry　of　building　units,　framework-framework　interaction,　and　so　forth,　have　also　been　taken　into　account　in　the　design　and　synthesis　of　stable　MOFs.　On　the　basis　of　these　approaches,　the　stability　of　resulting　MOFs　under　corresponding　conditions　has　been　remarkably　enhanced.　With　high　chemical　stability　achieved,　the　MOFs　have　found　many　new　and　significant　applications,　aiming　at　addressing　global　challenges　related　to　environmental　pollution,　energy　shortage,　and　food　safety.　A　series　of　stable　MOFs　have　been　constructed　for　detecting　and　eliminating　contaminations.　Various　fluorescent　MOFs　were　rationally　customized　to　be　powerful　platforms　for　sensing　hazardous　targets　in　food　and　water,　such　as　dioxins,　antibiotics,　veterinary　drugs,　and　heavy　metal　ions.　Some　hydrophobic　MOFs　even　showed　effective　and　specific　capture　of　low-concentration　volatile　organic　compounds.　Novel　MOFs　with　record-breaking　acid/base/nucleophilic　regent　resistance　have　expanded　their　application　scope　under　harsh　conditions.　BUT-8(Cr)A,　as　the　most　acid-stable　MOF　yet,　showed　reserved　structural　integrity　in　concentrated　H2SO4　and　recorded　high　proton　conductivity;　the　most　alkali-resistant　MOF,　PCN-601,　retained　crystallinity　even　in　boiling　saturated　NaOH　aqueous　solution,　and　such　base-stable　MOFs　composed　of　non-noble　metal　clusters　and　poly　pyrazolate　ligands　also　demonstrated　great　potential　in　heterogeneous　catalysis　in　alkaline/nucleophilic　systems　for　the　first　time.　It　is　believed　that　this　Account　will　provide　valuable　references　on　stable　MOFs＇　construction　as　well　as　application　expansion　toward　harsh　conditions,　thereby　being　helpful　to　promote　MOF　materials　to　step　from　fundamental　research　to　practical　applications.