diff --git a/pandas/core/internals/blocks.py b/pandas/core/internals/blocks.py
index 5f0b0aba2d17c..1ed7fe8a8dad2 100644
--- a/pandas/core/internals/blocks.py
+++ b/pandas/core/internals/blocks.py
@@ -668,6 +668,7 @@ def replace(
         #  go through replace_list
 
         values = self.values
+        value = self._standardize_fill_value(value)  # GH#45725
 
         if isinstance(values, Categorical):
             # TODO: avoid special-casing
diff --git a/pandas/tests/frame/methods/test_replace.py b/pandas/tests/frame/methods/test_replace.py
index 001a50c3ce1b0..f92c779c85f03 100644
--- a/pandas/tests/frame/methods/test_replace.py
+++ b/pandas/tests/frame/methods/test_replace.py
@@ -661,6 +661,21 @@ def test_replace_simple_nested_dict_with_nonexistent_value(self):
         result = df.replace({"col": {-1: "-", 1: "a", 4: "b"}})
         tm.assert_frame_equal(expected, result)
 
+    def test_replace_numpy_nan(self, nulls_fixture):
+        # GH#45725 ensure numpy.nan can be replaced with all other null types
+        to_replace = np.nan
+        value = nulls_fixture
+        dtype = object
+        df = DataFrame({"A": [to_replace]}, dtype=dtype)
+        expected = DataFrame({"A": [value]}, dtype=dtype)
+
+        result = df.replace({to_replace: value}).astype(dtype=dtype)
+        tm.assert_frame_equal(result, expected)
+
+        # same thing but different calling convention
+        result = df.replace(to_replace, value).astype(dtype=dtype)
+        tm.assert_frame_equal(result, expected)
+
     def test_replace_value_is_none(self, datetime_frame):
         orig_value = datetime_frame.iloc[0, 0]
         orig2 = datetime_frame.iloc[1, 0]
diff --git a/pandas/tests/series/methods/test_replace.py b/pandas/tests/series/methods/test_replace.py
index 6a8dacfda5e78..c852898a217a1 100644
--- a/pandas/tests/series/methods/test_replace.py
+++ b/pandas/tests/series/methods/test_replace.py
@@ -36,6 +36,23 @@ def test_replace_explicit_none(self):
         assert expected.iloc[-1] is None
         tm.assert_series_equal(result, expected)
 
+    def test_replace_numpy_nan(self, nulls_fixture):
+        # GH#45725 ensure numpy.nan can be replaced with all other null types
+        to_replace = np.nan
+        value = nulls_fixture
+        dtype = object
+        ser = pd.Series([to_replace], dtype=dtype)
+        expected = pd.Series([value], dtype=dtype)
+
+        result = ser.replace({to_replace: value}).astype(dtype=dtype)
+        tm.assert_series_equal(result, expected)
+        assert result.dtype == dtype
+
+        # same thing but different calling convention
+        result = ser.replace(to_replace, value).astype(dtype=dtype)
+        tm.assert_series_equal(result, expected)
+        assert result.dtype == dtype
+
     def test_replace_noop_doesnt_downcast(self):
         # GH#44498
         ser = pd.Series([None, None, pd.Timestamp("2021-12-16 17:31")], dtype=object)